Cosibelimab in advanced cutaneous squamous cell carcinoma (CSCC): Longer-term efficacy and safety results from pivotal study

BackgroundCosibelimab is a high-affinity, fully human monoclonal antibody that directly binds to programmed death ligand-1 (PD-L1) and blocks its interaction with the programmed death receptor-1 (PD-1) and B7.1 receptors to restore an anti-tumor immune response. Cosibelimab also has a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) as an additional mechanism of anti-tumor immunity. Efficacy and safety data from a pivotal study (NCT03212404) supported a biologics license application for cosibelimab for the treatment of patients (pts) with advanced CSCC (metastatic [mCSCC] or locally advanced [laCSCC]) who are not candidates for curative surgery or radiation. Here, we present new longer-term follow-up data from the pivotal study.MethodsPts with mCSCC (Group [Gp] 1) and laCSCC (Gp 2) were treated with cosibelimab 800 mg Q2W. The primary endpoint was objective response rate (ORR; complete response + partial response) by independent central review (ICR) assessed by Gp. The safety analysis included all CSCC pts treated with at least one dose and includes a third Gp of pts with mCSCC treated with cosibelimab 1200 mg Q3W (Gp 3).ResultsAs of the 31 March 2023 data cutoff, 192 pts were enrolled and treated (78 in Gp 1, 58 in Gp 2 and 56 in Gp 3), and 109 pts were eligible for long-term efficacy assessment (78 in Gp 1 and 31 in Gp 2). With a median duration of follow-up of 29.3 months (range: 0.4-52.0) for Gp 1 and 24.1 months (range: 2.8-37.3) for Gp 2, ORR per ICR was 50.0% (95% CI: 38.5-61.5) and 54.8% (95% CI: 36.0-72.7), respectively. The complete response rate was 12.8% and 25.8% for Gp 1 and 2, respectively. Median duration of response has not been reached in either Gp, with a probably of maintaining response at 24 months of 72.1% and 80.2% for Gp 1 and 2, respectively. The most common adverse events (AEs) by any grade (Gr) were fatigue (22.9%), anemia (20.3%), constipation (16.1%) and diarrhea (15.1%); Gr ≥ 3 were anemia (5.2%) and lipase increased (3.1%). 3.6% of pts experienced a Gr 3 immune-related AE (no Gr ≥ 4).ConclusionsCosibelimab demonstrates robust objective response and complete response rates in advanced CSCC, with manageable safety and notable low rates of overall and severe immune-related AEs.Clinical trial identificationNCT03212404.Legal entity responsible for the studyCheckpoint Therapeutics, Inc.FundingCheckpoint Therapeutics, Inc.DisclosureE. Muñoz-Couselo: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Personal, Advisory Role: Immunocore, Regeneron, Menarini, Roche; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics; Non-Financial Interests, Personal, Leadership Role: Gem, Grupo Español De Melanoma, Seom, Sociedad Española De Oncologia Medica. H. Montaudie: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, BMS, Pierre Fabre; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. M.A. Berciano Guerrero: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme, BMS, Eisai, Pierre Fabre, Eli Lilly, Novartis, PharmaMar; Financial Interests, Institutional, Research Funding: Novartis; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics. M.D.C. Alamo De La Gala, J. Charles, H. Shue, A. Tazbirkova, P. Clingan: Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. G. Quereux: Financial Interests, Personal, Speaker, Consultant, Advisor: Sanofi; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. C. Nardin: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Speaker, Consultant, Advisor, Board, consulting: BMS; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. R. Yaya Tur: Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. S. Dalle: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Personal, Stocks/Shares, Spouse Sanofi employee and stock owner: Sanofi; Financial Interests, Institutional, Research Grant: BMS, MSD, AstraZeneca. M. Beylot-Barry: Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. R. Ladwa: Financial Interests, Personal, Advisory Role, Speaker fees, advisory role/ consultancy: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role, Speaker fees, advisory role: Sanofi; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc; Financial Interests, Institutional, Other, Investigator initiated research: Merck Sharp & Dohme. M. McGrath: Financial Interests, Personal, Advisory Role, Speaker fee, advisory role: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. D. Brungs: Financial Interests, Personal, Advisory Board, Honoraria: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. D. Harris: Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc; Non-Financial Interests, Personal, Member: ASCO, AGITG, NZSO. S.J. Fourie: Financial Interests, Personal, Speaker, Consultant, Advisor, Speaker Honoraria: Merck Sharp & Dohme, Roche, Sanofi, MundiPharma; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics; Financial Interests, Personal, Member of Board of Directors: ICON Oncology Holdings Pty(Ltd), Gamma Knife South Africa; Financial Interests, Personal, Member of Board of Directors, Board member and equity interest: Drs Alberts Bouwer Jordaan Inc. D.R. Malan: Financial Interests, Personal, Member of Board of Directors: Phoenix Pharma; Financial Interests, Institutional, Principal Investigator: Checkpoint Therapeutics, Inc. J. Oliviero: Financial Interests, Personal, Officer, Officer and ownership interest: Checkpoint Therapeutics, Inc.